Browsing by Author "Liu, Yining"

Now showing 1 - 4 of 4

Open Access
A Balance between Pro-Inflammatory and Pro-Reparative Macrophages is Observed in Regenerative D-MAPS.
(Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2023-04) Liu, Yining; Suarez-Arnedo, Alejandra; Shetty, Shamitha; Wu, Yaoying; Schneider, Michelle; Collier, Joel H; Segura, Tatiana
Microporous annealed particle scaffolds (MAPS) are a new class of granular materials generated through the interlinking of tunable microgels, which produce an interconnected network of void space. These microgel building blocks can be designed with different mechanical or bio-active parameters to facilitate cell infiltration and modulate host response. Previously, changing the chirality of the microgel crosslinking peptides from L- to D-amino acids led to significant tissue regeneration and functional recovery in D-MAPS-treated cutaneous wounds. In this study, the immunomodulatory effect of D-MAPS in a subcutaneous implantation model is investigated. How macrophages are the key antigen-presenting cells to uptake and present these biomaterials to the adaptive immune system is uncovered. A robust linker-specific IgG2b/IgG1 response to D-MAPS is detected as early as 14 days post-implantation. The fine balance between pro-regenerative and pro-inflammatory macrophage phenotypes is observed in D-MAPS as an indicator for regenerative scaffolds. The work offers valuable insights into the temporal cellular response to synthetic porous scaffolds and establishes a foundation for further optimization of immunomodulatory pro-regenerative outcomes.
Open Access
Anti-Cytokine Active Immunotherapy Based on Supramolecular Peptides for Alleviating IL-1β-Mediated Inflammation.
(Advanced healthcare materials, 2024-08) Shetty, Shamitha; Wu, Yaoying; Lloyd, Christopher Z; Mehta, Nalini; Liu, Yining; Woodruff, Mia E; Segura, Tatiana; Collier, Joel H
IL-1β is a principal proinflammatory cytokine underlying multiple local and systemic chronic inflammatory conditions including psoriasis, rheumatoid arthritis, inflammatory bowel disease, and type 2 diabetes. Passive immunotherapies and biologic drugs targeting IL-1β, while offering significant clinical benefit, nevertheless have limitations such as significant non-response rates, induction of anti-drug antibodies, and high costs. Here, an active immunotherapy raising antibody responses against IL-1β employing self-assembling peptide nanofibers is described. The nanofibers contain defined quantities of B-cell epitopes from IL-1β and exogenous T helper epitopes and employ the Q11 self-assembling peptide platform. Without adjuvant, the nanofibers raised durable anti-IL-1β antibody responses that inhibit IL-1β activity in vitro and in vivo. In a mouse model of imiquimod-induced psoriasis, prophylactic immunizations with the nanofibers diminished symptoms of epidermal thickening. This therapeutic effect is associated with biasing the immune response toward an anti-inflammatory IgG1/Th2 phenotype and a lowered expression of proinflammatory genes in the skin. Further, anti-IL-1β nanofibers induced therapeutic immunosuppressive CD62L+ Treg cells. This technology represents a potential alternative for passive immunotherapies and other biologics for treating chronic inflammatory conditions.
Open Access
Biomaterials-Mediated Regulation of Macrophage Cell Fate.
(Frontiers in bioengineering and biotechnology, 2020-01) Liu, Yining; Segura, Tatiana
Endogenous regeneration aims to rebuild and reinstate tissue function through enlisting natural self-repairing processes. Promoting endogenous regeneration by reducing tissue-damaging inflammatory responses while reinforcing self-resolving inflammatory processes is gaining popularity. In this approach, the immune system is recruited as the principal player to deposit a pro-reparative matrix and secrete pro-regenerative cytokines and growth factors. The natural wound healing cascade involves many immune system players (neutrophils, macrophages, T cells, B cells, etc.) that are likely to play important and indispensable roles in endogenous regeneration. These cells support both the innate and adaptive arms of the immune system and collectively orchestrate host responses to tissue damage. As the early responders during the innate immune response, macrophages have been studied for decades in the context of inflammatory and foreign body responses and were often considered a cell type to be avoided. The view on macrophages has evolved and it is now understood that macrophages should be directly engaged, and their phenotype modulated, to guide the timely transition of the immune response and reparative environment. One way to achieve this is to design immunomodulating biomaterials that can be placed where endogenous regeneration is desired and actively direct macrophage polarization. Upon encountering these biomaterials, macrophages are trained to perform more pro-regenerative roles and generate the appropriate environment for later stages of regeneration since they bridge the innate immune response and the adaptive immune response. This new design paradigm necessitates the understanding of how material design elicits differential macrophage phenotype activation. This review is focused on the macrophage-material interaction and how to engineer biomaterials to steer macrophage phenotypes for better tissue regeneration.
Open Access
Modulating Macrophage Response with Microporous Annealed Particle Scaffolds
(2022) Liu, Yining
When designing biomaterials for clinical applications, the performance of these platforms hinges on their interaction with the host immune system. A failure in engaging and incorporating the correct immune response would lead to foreign body response and subsequent rejection of the materials. To improve the biocompatibility of biomaterials and avoid undesired immune reactions, the key immunomodulatory cell type macrophage needs to be engaged and its phenotype modulated properly and timely. Therefore, the design parameters of biomaterials should be carefully considered in the context of macrophage modulation. Microporous annealed particle scaffolds (MAPS) are a new class of immunomodulatory granular materials generated through the interlinking of microgels. The modular nature of MAPS offers enormous tunability in not only the individual microgel design but also the homogenous or heterogenous microgel assembly into the bulk scaffold. We leveraged the plug-and-play feature of MAPS to study the effect of two design parameters, microgel crosslinking peptide (comprised of L- or D-amino acids) and spatial confinement (achieved through varying microgel size), on macrophage modulation and host responses. We uncovered that a fine balance between pro-regenerative and pro-inflammatory macrophage phenotypes in MAPS with D-amino acid-based crosslinker was an indicator for regenerative scaffolds in a subcutaneous implantation model. We also discovered that scaffolds comprised of large microgels with pore size that can accommodate ~40 µm diameter spheres induced a more balanced pro-regenerative macrophage response and better wound healing outcomes with more mature collagen regeneration and reduced inflammation level. The role of spatial confinement on macrophage response was further explored in vitro, where we demonstrated that size-dependent macrophage response to M1/M2 cytokine stimulations was tied to the change in cell morphology and motility. This work offers valuable insights into the dynamic immune response to synthetic porous scaffolds with a specific focus on macrophages, and establishes a foundation for further optimization of immunomodulatory pro-regenerative outcomes for would healing and biomaterial implants.